Differential Contribution of Endothelial Function to Vascular Reactivity in Conduit and Resistance Arteries From Deoxycorticosterone-Salt Hypertensive Rats

Hypertension ◽  
1996 ◽  
Vol 27 (6) ◽  
pp. 1245-1253 ◽  
Author(s):  
Richard M. White ◽  
Carlos O. Rivera ◽  
Cathy Bruner Davison
Keyword(s):  
Endothelial Function ◽  
Vascular Reactivity ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
Differential Contribution

Benidipine Improves Endothelial Function in Renal Resistance Arteries of Hypertensive Rats

Hypertension ◽  
1996 ◽  
Vol 28 (1) ◽  
pp. 58-63 ◽  
Author(s):  
Yasuaki Dohi ◽  
Masayoshi Kojima ◽  
Koichi Sato
Keyword(s):  
Endothelial Function ◽  
Resistance Arteries ◽  
Hypertensive Rats

Abstract P267: Arbidol, A Targeted Covid-19 Therapy, Inhibited Contractile Responses To Phenylephrine In Mesenteric Arteries And Aortas Of Hypertensive Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Olufunke O Arishe ◽  
Stephanie Wilczynski ◽  
Anna Thamasett ◽  
Clinton R Webb
Keyword(s):  
Lipid Membranes ◽  
Vascular Reactivity ◽  
Viral Infections ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Adrenergic Stimulation ◽  
Hypertensive Rats ◽  
Contractile Responses ◽  
Viral Attachment

Background: Hypertension is the most prevalent comorbidity of COVID-19 infection. This infection is caused by the severe acute respiratory syndrome coronavirus SARS-CoV-2. SARS-CoV-2 is a single-stranded RNA and could activate the endosomal Toll-like receptor 7 (TLR7), indicating a vital role of the receptor in its therapeutic target. Studies have reported that the lysosomotropic drug chloroquine has antihypertensive effects through its action on inhibiting the endosomal TLRs. Arbidol is a potential broad-spectrum antiviral used in the treatment of many viral infections including influenza. Arbidol prevents viral infection by interacting with aromatic acids; arbidol also binds to lipid membranes, altering the configuration of the cytoplasm or endosome. Wang et al., in 2020 reported that arbidol effectively inhibited the coronavirus SARS-CoV-2 in vitro by impeding viral attachment and release from the endolysosomes. Hypothesis: We hypothesized that arbidol would improve vascular reactivity in hypertension. Methods: We studied the effects of arbidol on the contractility of mesenteric resistance arteries (MRA) and aortas of male Wistar rats (20 weeks old, n=4) and spontaneously hypertensive rats (SHR) (20 weeks old, n=4) on a myograph by incubating the arterial rings with 10μM arbidol (Sigma, USA.) or vehicle (DMSO) for 30 mins. Statistical analysis was performed using nonlinear regression, and one- and two-way ANOVAs. Results: Arbidol (10 μM) impaired the contractile responses of MRA and aorta from normotensive and hypertensive rats to phenylephrine (PE). MRA Wistar: (pEC50 6.11 ± 0.15 vs 3.42 ± 0.38), SHR: (5.89 ± 0.19 vs 3.56 ± 0.19) and aorta Wistar: (pEC 50 7.49 ± 0.19 vs 5.97 ± 0.14), SHR (pEC50 7.14 ± 0.31 vs 4.41 ± 0.15). The arbidol-induced impaired contraction to PE was greater in the SHR aorta compared with the Wistar aorta. After washing out the drug, the arterial rings contracted to 120mM KCl at the same magnitude as the initial contraction to 120mM KCl. Conclusions: Our data demonstrate that arbidol impairs vascular contractile responses to α-adrenergic stimulation, with a greater response in the hypertensive rats. This indicates antihypertensive effects potentially through the regulation of TLR signaling.

Abstract 55: Hiv Viral Proteins Elevate Blood Pressure And Impairs Endothelial Function In Resistance Arteries Via Sex Specific, Immune And Nox1-dependent Mechanisms In Mice.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Taylor Kress
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Viral Infection ◽  
Immune Cells ◽  
Vascular Reactivity ◽  
Radio Telemetry ◽  
Viral Proteins ◽  
Mesenteric Arteries ◽  
Resistance Arteries

Thanks to the onset of combination antiretroviral therapy (cART), patients living with HIV live longer but experience accelerated rates of hypertension. However, the etiology of HIV-associated hypertension remains ill defined, specifically the respective contributions of repressed viral infection and cART treatment. Herein, we took advantage of a transgenic model (Tg26) of repressed viral infection to investigate the contribution of HIV viral proteins to hypertension. Quantification of inflammatory cytokines revealed elevated circulating TNFα levels but also high aorta and intraperitoneal immune cells TNFα in male Tg26 mice leading to the hypothesis that HIV-associated hypertension involves immune-derived TNFα secretion and endothelial dysfunction in males and females Tg26 mice. Blood pressure (BP) was measured via radio telemetry and vascular reactivity studies performed via wire myography. BP analysis revealed increased mean arterial pressure (MAP: male: WT=112.3±1.3 vs Tg26=121.9±4.0 mmHg/ female: WT=110.6±3.01/ Tg26=120.3±6.9 mmHg) and heart rate in both sexes (P<0.05). However, blockade of TNFα action with etanercept restored BP and aortic endothelial function in male Tg26 mice only. Along with an increase in TNFα, male Tg26 aortas showed infiltration of Tcells and proinflammatory cytokines IL-18, and IL-6, which were not seen in females. However, scavenging of reactive oxygen species with the selective NOX1 inhibitor GKT771 restored aorta endothelial function in both sexes. A contributor to hypertension is impaired endothelial relaxation in resistance arteries. Mesenteric arteries showed impaired endothelial relaxation to acetylcholine in both male and female Tg26 mice (P<0.05) with no impairment in smooth muscle cell relaxation. This phenotype was reproduced in WT mice transplanted with Tg26 bone marrow (BM) and remarkably reversed in Tg26 mice receiving WT BM supporting a clear role for immune cells in endothelial dysfunction. Collectively, these data indicate that HIV-related hypertension involves immune and NOX1-dependent endothelial dysfunction in both sexes but TNFα-dependent mechanisms in males only providing evidence of sex specific mechanisms.

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